Clinical Research Directory

Genotypic Influences on Network Progression in Parkinson's Disease

In this longitudinal study, the investigators will follow Parkinson's disease (PD) patients with and without glucocerebrosidase (GBA) mutations. The investigators hypothesize that the rate of increase in brain network activity over time (network progression rate) is faster in patients with GBA gene mutations.

Agricultural Health Study Follow-up

Background: \- The Agricultural Health Study (AHS) is looking at the long-term health effects of farming exposures including pesticides, crops, and animals. The chronic health effects of exposure to pesticides are easier to study in farmers and their spouses. They know what chemicals they use and tend to live in the same place for most of their adult lives. AHS participants are expected to report any changes in their health. This includes any new medical conditions. Researchers want to follow up on these reports to confirm their accuracy. Objectives: \- To follow up AHS participants who have self-reported that they have a new disease and confirm their diagnosis. Eligibility: \- Current AHS participants. Design: * Researchers will confirm self-reported changes in medical conditions by contacting the AHS participant to ask for more information. * The AHS participant will give permission for researchers to contact their doctor to look at their medical records. They will also be asked to provide a cheek swab or saliva sample. * Diseases of interest are rheumatoid arthritis, lupus, and Sjogren s Syndrome. Other diseases will be followed up in the future. Other diseases will be followed up in the future....

Deep Brain Stimulation Surgery for Movement Disorders

Background: \- Deep brain stimulation (DBS) is an approved surgery for certain movement disorders, like Parkinson's disease, that do not respond well to other treatments. DBS uses a battery-powered device called a neurostimulator (like a pacemaker) that is placed under the skin in the chest. It is used to stimulate the areas of the brain that affect movement. Stimulating these areas helps to block the nerve signals that cause abnormal movements. Researchers also want to record the brain function of people with movement disorders during the surgery. Objectives: * To study how DBS surgery affects Parkinson s disease, dystonia, and tremor. * To obtain information on brain and nerve cell function during DBS surgery. Eligibility: \- People at least 18 years of age who have movement disorders, like Parkinson's disease, essential tremor, and dystonia. Design: * Researchers will screen patients with physical and neurological exams to decide whether they can have the surgery. Patients will also have a medical history, blood tests, imaging studies, and other tests. Before the surgery, participants will practice movement and memory tests. * During surgery, the stimulator will be placed to provide the right amount of stimulation for the brain. Patients will perform the movement and memory tests that they practiced earlier. * After surgery, participants will recover in the hospital. They will have a followup visit within 4 weeks to turn on and adjust the stimulator. The stimulator has to be programmed and adjusted over weeks to months to find the best settings. * Participants will return for followup visits at 1, 2, and 3 months after surgery. Researchers will test their movement, memory, and general quality of life. Each visit will last about 2 hours.

PET Imaging of Cyclooxygenases in Neurodegenerative Brain Disease

Background: About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation. Objective: To learn whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers. Eligibility: Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, Huntington s disease, or MCI, ALS and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181. Design: Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neuropsychological testing. Their heart function will be measured. Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs. Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan. Participants will have 2-5 study visits. Participation lasts 1 week to 4 months, depending on scheduling.

Study of the Link Between Freezing of Gait and Oropharyngeal Freezing in Parkinson's Patients

Parkinson's Disease: Study of the Link Between Gait Freezing and Oropharyngeal Freezing Parkinson's disease is the second most common neurodegenerative disorder worldwide. Parkinsonian dysphagia is a frequently encountered disorder in this condition, affecting all phases of swallowing: oral, pharyngeal, and esophageal. This dysphagia can occur at any stage of the disease. While most swallowing difficulties develop in the advanced stages of Parkinson's disease, they can also appear early on and are often underdiagnosed. The prevalence of swallowing disorders in Parkinson's disease is estimated to range from 40% to 80%, with this variability explained by the significant differences in the precision of swallowing evaluations conducted and the fact that dysphagia is still too frequently underdiagnosed. Yet, dysphagia is the leading cause of mortality in Parkinson's patients. Dysphagia can negatively affect patients' quality of life. It leads to difficulties during oral intake (food, liquids, and medications), weight loss, dehydration, malnutrition, and limitations in social activities. Depression is frequently associated with reduced quality of life in Parkinson's patients with swallowing disorders. Moreover, aspiration pneumonia due to mis-swallowing is one of the primary reasons for hospitalization in Parkinson's patients, potentially leading to severe complications and, at times, death. Oropharyngeal freezing, also called oral festination, is an involuntary, repetitive anteroposterior movement of the tongue against the soft palate performed before transferring the food bolus to the pharynx. This movement is also observed during multiple swallows. This phenomenon is more frequent in dysphagic Parkinson's patients, yet its impact on swallowing dynamics remains poorly understood. Oropharyngeal freezing has been observed in approximately 40% to 75% of Parkinson's patients during videofluoroscopic swallow studies, also known as swallowing pharyngography. Oropharyngeal freezing inhibits the initiation of swallowing, keeping the airway open and leading to tracheal aspiration of residues. Some fragments then slide into the valleculae and pyriform sinuses. Thus, oropharyngeal freezing exacerbates pharyngeal phase incoordination, increasing the risk of aspiration pneumonia. Therefore, addressing this swallowing disorder is essential. Oropharyngeal freezing is intrinsically rhythmic. While limited studies have been conducted on the topic, they agree that gait freezing (difficulty initiating walking, stopping in response to obstacles, or circumventing them) and oropharyngeal freezing share common pathophysiological mechanisms. Gait freezing is not limited to deficits in the locomotor network but is part of a broader deficit affecting spatiotemporal coordination in various tasks, similar to oropharyngeal freezing. It is, therefore, crucial to detect this oral phase swallowing disorder as early as possible, enabling tailored early intervention that helps patients maintain their swallowing abilities for as long as possible and prevents complications mentioned earlier. Since gait freezing is diagnosed much earlier and more systematically, it would be interesting to investigate whether there is a correlation between the presence of gait freezing and oropharyngeal freezing in these patients. This could guide patients with gait freezing toward early speech-language assessments to evaluate the presence of oropharyngeal freezing. The objectives of the study are examine the prevalence of oropharyngeal freezing in Parkinson's patients. Based on the results obtained from the NFOG-Q (New Freezing of Gait Questionnaire), two groups will be formed: The first group will consist of patients exhibiting gait freezing. The second group will consist of patients without gait freezing. The secondary objectives of the study are examine the common characteristics between these two types of freezing (gait and oropharyngeal). To assess the sensitivity and reliability of the NFOG-Q in detecting oropharyngeal freezing.To determine the prevalence of oropharyngeal freezing based on the score obtained on the UPDRS (Unified Parkinson's Disease Rating Scale). To analyze the link between patients' rhythmic abilities and the presence or absence of one or both types of freezing.

Efficacy of Repetitive Transcranial Magnetic Stimulation for Improving Depressive Symptoms in Patients With Parkinson's Disease

The purpose of this study is to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving depressive symptoms in patients with Parkinson's Disease(PD). Participants will be randomly assigned to either an active rTMS group or a sham-control group. The study aims to evaluate the efficacy and feasibility of a neuronavigation-guided bilateral M1 rTMS protocol.

PET Scanning in Parkinson s Disease

This is an in vivo positron emission tomography (PET) study of regional cerebral dopamine and blood flow in normal volunteers, persons with Parkinson s disease (both familial and sporadic), and those with schizophrenia spectrum disorders. The latter also sign consent for NIH approved protocol 89-M-0160, "Inpatient Evaluation of Neuropsychiatric Patients," PI: Daniel Eisenberg, M.D. Using PET with 6-\[F-18\] Fluoro-L-dopa (FDOPA) and (15)0-H2O in a single scan session, both presynaptic dopaminergic function and regional cerebral blood flow (rCBF) are assessed. The kinetic rate constant (Ki) for presynaptic dopaminergic uptake in striatum and other regions is calculated. We compare Ki across subject groups and relate the findings to rCBF. Findings are also related to allelic variation in genes of interest, for determination of which participants sign separate consent for NIH approved protocol 95-M-0150 Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings, PI: Karen F. Berman, MD. We also draw comparisons between subjects with inherited vs. sporadic Parkinson s disease to determine whether the PET phenotype is the same in both groups, and we compare system-level, circuit-based pathophysiology across PD and schizophrenia groups. Each subject is further screened with an MRI to rule out structural abnormalities and also to further delineate areas of interest in the PET scans....

Neural Mechanisms of Aerobic Exercise Benefits in PD With DBS

This study is focused on people with Parkinson's disease who already have deep brain stimulation devices. The goal is to understand how aerobic exercise, specifically forced vs voluntary cycling, affects movement, thinking, and brain activity in these individuals. Parkinson's disease is a progressive condition that impacts both movement and cognitive function. Previous research suggests aerobic exercise can improve PD symptoms, but the mechanisms underlying the improvement are not fully understood. This study aims to evaluate the neural (brain) mechanisms underlying exercise.

Physiological Investigations of Movement Disorders

Background: * Previous studies have given researchers information on how the brain controls movement, how people learn to make fine, skilled movements, and why some people have movement disorders. However, further research is needed to learn more about the causes of most movement disorders, such as Parkinson's disease. * By using small, specialized studies to evaluate people with movement disorders and compare them with healthy volunteers, researchers hope to learn more about the changes in the brain and possible causes of movement disorders. Objectives: * To better understand how the brain controls movement. * To learn more about movement disorders. * To train movement disorder specialists. Eligibility: * Individuals 18 years of age or older who have had a movement disorder diagnosed by a neurologist and are able to participate based on the specific requirements of the small study. * Healthy volunteers 18 years of age or older. Design: * Participants will have a screening visit with medical history, physical examination, and questionnaire to determine eligibility. Eligible participants will give consent to participate in up to seven additional outpatient visits for study procedures. The number of sessions and the procedures needed for participation depend on specific symptoms. * Participants must avoid drinking alcohol or caffeinated drinks (sodas, coffee, and tea) for at least 2 days (48 hours) before each session. * Potential studies may include magnetic resonance imaging (MRI) scans, functional MRI scans, electroencephalography, magnetoencephalography, transcranial magnetic stimulation, nerve and sensory stimulation, or movement and mental tasks during any of the above procedures. * This study does not provide treatment for movement disorders. Participants will not have to stop any treatment in order to participate.

Clinical Laboratory Evaluation of Chronic Autonomic Failure

Background: The autonomic nervous system controls automatic body functions. Researchers want to improve the tests used to diagnose autonomic failure. Orthostatic hypertension is a drop in blood pressure when a person stands up. Researchers want to focus on this sign of autonomic failure. Objective: To improve testing for conditions that cause autonomic nervous system failure. Eligibility: People ages 18 and older in one of these categories: * Their blood pressure drops when they get up. * They have had a heart transplant or bilateral endoscopic thoracic sympathectomies or have had or will have renal sympathetic ablation Design: All participants will be screened with: * Medical history * Physical exam * Blood and urine tests Some participants will be screened with: * Heart and breathing tests * IV placement into an arm vein * Tilt table testing: Participants lie on a table that tilts while an IV is used to draw their blood. Participants may stay in the hospital for up to 1 week depending on their tests. Tests may include repeats of screening tests and: * Sweat testing: A drug is placed on the skin to cause sweating. Sensors on the skin measure moisture. * Lumbar puncture: A needle is inserted between the bones in the back to collect fluid. * MRI and PET/CT scan: Participants lie on a table that slides into a scanner. For the PET/CT, a small amount of a radioactive chemical will be injected with a small amount of a radioactive chemical. * Bladder catheter placement to collect urine * Skin biopsies: A punch tool removes a small skin sample. * Tests to see how the pupils react to light * Smelling tests * Thinking and memory tests * Questionnaires Participants may have a visit about 2 years later to repeat tests.

Telerehabilitation in People With Parkinson's Disease

Although TeleRehabilitation (TR) is widely accepted as an appropriate model for the provision of professional health services in the field of physiotherapy, with already established standards, guidelines and policies, there are still few studies in the literature on the use of TR as a rehabilitation tool in people with Parkinson's Disease (PD). Therefore, further studies on the efficacy of TR in the management of motor and non-motor symptoms of PD are needed. The study TEMPO aims at assessing the efficacy (in terms of autonomy in carrying out the activities of daily life) of a home TR program based on serious games in people with PD compared to conventional day-hospital treatment.

Prevent Cognitive Decline in GBA-associated Parkinson's Disease

This is a proof-of-concept trial to investigate the efficacy of prasinezumab to slow or prevent cognitive decline in people with Parkinson's disease carrying a severe mutation in the GBA (glucocerebrosidase) gene. The duration of the intervention per patient will be 104 weeks with monthly infusions. The investigators plan to enroll 120 participants (60 participants per treatment arm). This study will be conducted across Europe in the following countries: France, Germany, Italy, Luxembourg, Spain, Sweden, UK.

A Multicenter Study to Evaluate Safety, Tolerability, and Clinical Responses of DSP-1083 Into Subjects With Parkinson's Disease

The Goal of this study is to evaluate the safety, tolerability, and clinical responses following implantation of DSP-1083. Study enrolls both male and female patients in 2 cohorts. This study will be held in approximately 5-8 study sites in United States

ExAblate Transcranial MRgFUS for Unilateral Pallidotomy for the Treatment of Parkinson's Disease

The proposed study is to evaluate the safety and initial effectiveness of the ExAblate Transcranial MRgFUS) treatment of patients with L-dopa induced dyskinesia of Parkinson's disease (LID PD). Safety: To evaluate the incidence and severity of adverse events associated with ExAblate Transcranial 4000 MRgFUS treatment of dyskinesia of Parkinson's disease. Effectiveness: To determine the level of effectiveness of the ExAblate Transcranial MRgFUS treatment of LID in PD patients. Efficacy will be determined utilizing clinical rating scales for dyskinesia (UPDRS-IV and the Unified Dyskinesia Rating Scale) from examinations at Baseline, 3-Months and 12-Months post-ExAblate treatment.

Study to Test Effects and Safety of RO7568282 in Early Parkinson's Disease

The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of RO7568282 compared with placebo in participants with early-stage Parkinson's disease (PD) on stable symptomatic monotherapy with levodopa.

Utilization of Aerobic Exercise to Maintain Neurologic Health

A promising approach to combat the protein aggregation, oxidative stress, and neuroinflammation occurring with PD is consistent aerobic exercise. Dr. Alberts' recently completed Phase III Randomized Clinical Trial2,3 demonstrating that a specific aerobic exercise prescription was effective at slowing the progression of motor symptoms in mild to moderate Parkinson's disease patients. This project extends our positive findings by evaluating the effectiveness of this PD-specific exercise intervention in individuals identified as high-risk of converting to PD. The underlying hypothesis is that aerobic exercise can delay or prevent motor and cognitive decline associated with PD, as aerobic exercise is known to reduce oxidative stress and neuroinflammation and enhance mitochondria function.

Deep Brain Stimulation Therapy in Movement Disorders

Background: \- In deep brain stimulation (DBS), a device called a neurostimulator is placed in the chest. It is attached to wires in parts of the brain that affect movement. DBS might help people with movement disorders like Parkinson s disease (PD), dystonia, and essential tremor (ET). Objective: \- To provide DBS treatment to people with some movement disorders. Eligibility: \- Adults 18 years and older with PD, ET, or certain forms of dystonia. Design: * Participants will be screened with medical history and physical exam. They will have blood and urine tests and: * MRI brain scan. The participant will lie on a table that slides in and out of a metal cylinder with a magnetic field. They will be in the scanner about 60 minutes. They will get earplugs for the loud noises. During part of the MRI, a needle will guide a thin plastic tube into an arm vein and a dye will be injected. * Electrocardiogram. Metal disks or sticky pads will be placed on the chest, arms, and legs. They record heart activity. * Chest X-ray. * Tests of memory, attention, concentration, thinking, and movement. * Eligible participants will have DBS surgery. The surgery and hospital care afterward are NOT part of this protocol. * Study doctors will see participants 3 4 weeks after surgery to turn on the neurostimulator. * Participants will return every month for 3 months, then every 3 months during the first year, and every 6 months during the second year. Each time, participants will be examined and answer questions. DBS placement will be evaluated with MRI. The neurostimulator will be programmed. At two visits, participants will have tests of movements, thinking, and memory.

A Study to Evaluate the Safety, Tolerability and Efficacy of MT101-5 in Subjects With Early Parkinson's Disease

A Phase IIa, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Efficacy of MT101-5 in Subjects with Early Parkinson's Disease. Primary objective of the study is to evaluate the safety and tolerability of MT101-5 400 mg and 600 mg oral tablet total daily dose compared to Placebo in subjects with Parkinson's Disease.

A Clinical Trial of LY3962681 in Healthy Volunteers and in Patients With Parkinson's Disease

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) of LY3962681 in healthy volunteers and patients with Parkinson's disease. The study consists of two parts, the Single Ascending Dose (SAD) study and the Multiple Ascending Dose (MAD) study. During the SAD portion of the study, healthy volunteers will receive a single dose of LY3962681 or placebo (artificial cerebrospinal fluid \[aCSF\]) administered intrathecally (into the spinal fluid). During the MAD portion of the study, patients with Parkinson's disease will receive two doses of either LY3962681 or placebo (aCSF) administered intrathecally (into the spinal fluid), 12 to 24 weeks apart. * The treatment period in the SAD study will be 1 day. The treatment period in the MAD study will be 2 dosing days, 12 to 24 weeks apart. * The follow-up period in the SAD study will be up to 52 weeks. The follow-up period in the MAD study will be up to 52 weeks after Dose 2.

Distinguishing Between Alzheimer's Disease, Lewy Body Dementia, and Parkinson's Disease

The study is designed to characterize the clinical, neuropsychological, polysomnographic, and neuroimaging findings among subjects with Alzheimer's disease, Lewy Body dementia, and Parkinsons' Disease.

Registry of Deep Brain Stimulation With the VERCISE™ System: Vercise DBS Registry

The purpose of this registry is to compile characteristics of world-wide outcomes for the use of Boston Scientific's commercially available Vercise DBS System in the treatment of Parkinson's disease. The utilization of Image Guided Programming (IGP), and other commercially available programming features, used as planning tools for the programming of patients with Boston Scientific's Vercise DBS System are also evaluated. Additionally, the utilization of the DBS Illumina 3D feature that may be used for the programming of patients with Boston Scientific's Vercise DBS Systems is also evaluated.

Intraoperative Microelectrode Recordings Using MAVEN Compared to Standard Recording Apparatuses

The purpose of this research is to determine if the electrophysiologic data collected from standard-of-care microelectrode recordings during human deep brain stimulation (DBS) surgery will be the same using the MAVEN device compared with the standard Alpha Omega device with either a tungsten standard-of-care microelectrode (for microelectrode recordings), or a carbon-fiber microelectrode (for neurotransmitter recordings). The number of microelectrodes used for both the tungsten and the carbon-fiber version will be the same as the standard-of-care.

Terazosin And Metabolic Engagement in Parkinson's Disease

To assess target engagement of terazosin (TZ) at multiple doses (1 mg/day, 3 mg/day, and 5 mg/day) and to assess sustained target engagement over 6 months relative to placebo in patients with Parkinson's Disease (PD). Target engagement will be measured using a whole blood luminescence assay to quantify Adenosine Triphosphate (ATP) and a plasma metabolomics assay. A subset of randomized participants will also undergo imaging studies to quantify cerebral ATP using 31P-magnetic resonance spectroscopy (31P-MRS) and 18F-fluurodeoxyglucosed positron emission tomography (18F-FDG PET) to assess changes in glucose uptake in response to TZ. The investigators will compare the mean change from baseline in these assays between the TZ and placebo groups. The null hypothesis to be tested is that TZ does not engage its target (phosphoglycerate kinase 1, or PGK1) and does not lead to increases in the outcome variables of interest. A total of 100 patients with early PD will be recruited. Participants will be randomized to TZ or placebo in a 60:40 fashion to account for predicted dropouts in the TZ group. Study treatment will be administered for 26 weeks, followed by a four-week washout period.

Feasibility and Safety of a Portable Exoskeleton to Improve Mobility in Parkinson's Disease

Physical therapy approaches for balance and walking deficits in Parkinson's disease (PD) have limited effectiveness, with mostly short-lasting benefits. An exoskeleton is a device that straps to the legs and provides a passive force to assist people to better ambulate. The goal of this study is to establish the feasibility and safety of a lightweight exoskeleton on mobility and fall reduction in people with PD. As most PD patients eventually require assistive mobility devices, the exoskeleton represents a new option for increased, mobility, quality of life, and independence. Qualified subjects will come to the clinic twice weekly for eight weeks (16 total visits) and wear the exoskeleton device while walking under the supervision of a trained kinesiotherapist. Study staff will also interview participants and assess their PD symptoms, quality of life, and overall mobility. This study hopes to establish exoskeletons as modern, standard of care devices, which allow people with PD to maintain more independent and productive lives.